Diagnosis and operative treatment of syndesmotic ankle injuries remain challenging due to the limitations of 2-dimensional imaging. The aim of this study was therefore to develop a reproducible method to quantify the displacement of a syndesmotic lesion based on 3-dimensional computed imaging techniques. Eighteen patients with a unilateral syndesmotic lesion were included. Bilateral imaging was performed with weightbearing cone-beam computed tomography (CT) in case of a high ankle sprain (n = 12) and by nonweightbearing CT in case of a fracture-associated syndesmotic lesion (n = 6). The healthy ankle was used as a template after being mirrored and superimposed on the contralateral ankle. The following anatomical landmarks of the distal fibula were computed: the most lateral aspect of the lateral malleolus and the anterior and posterior tubercle. The change in position of these landmarks relative to the stationary, healthy fibula was used to quantify the syndesmotic lesion. A control group of 7 studies was used. The main clinical relevant findings demonstrated a statistically significant difference between the mean mediolateral diastasis of both the sprained (mean [SD], 1.6 [1.0] mm) and the fracture group (mean [SD], 1.7 [0.6] mm) compared to the control group ( P < .001). The mean external rotation was statistically different when comparing the sprained (mean [SD], 4.7 [2.7] degrees) and the fracture group (mean [SD], 7.0 [7.1] degrees) to the control group ( P < .05). This study evaluated an effective method for quantifying a unilateral syndesmotic lesion of the ankle. Applications in clinical practice could improve diagnostic accuracy and potentially aid in preoperative planning by determining which correction needs to be achieved to have the fibula correctly reduced in the syndesmosis. Level III, retrospective comparative study.